Delta-6 desaturase FADS2 is a tumor-promoting factor in cholangiocarcinoma

IF 4.5 2区医学 Q1 ONCOLOGY Cancer Science Pub Date : 2024-08-07 DOI:10.1111/cas.16306

Kohsei Hasegawa, Haruna Fujimori, Kohta Nakatani, Masatomo Takahashi, Yoshihiro Izumi, Takeshi Bamba, Mao Nakamura-Shima, Rie Shibuya-Takahashi, Mai Mochizuki, Yuta Wakui, Makoto Abue, Wataru Iwai, Daisuke Fukushi, Kennichi Satoh, Kazunori Yamaguchi, Norihisa Shindo, Jun Yasuda, Naoki Asano, Takayuki Imai, Yukinori Asada, Yukio Katori, Keiichi Tamai

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Abstract

Cholangiocarcinoma is a fatal disease with limited therapeutic options. We screened genes required for cholangiocarcinoma tumorigenicity and identified FADS2, a delta-6 desaturase. FADS2 depletion reduced in vivo tumorigenicity and cell proliferation. In clinical samples, FADS2 was expressed in cancer cells but not in stromal cells. FADS2 inhibition also reduced the migration and sphere-forming ability of cells and increased apoptotic cell death and ferroptosis markers. Lipidome assay revealed that triglyceride and cholesterol ester levels were decreased in FADS2-knockdown cells. The oxygen consumption ratio was also decreased in FADS2-depleted cells. These data indicate that FADS2 depletion causes a reduction in lipid levels, resulting in decrease of energy production and attenuation of cancer cell malignancy.

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δ-6去饱和酶FADS2是胆管癌的促癌因子。

胆管癌是一种致命疾病，但治疗方法有限。我们筛选了胆管癌致瘤性所需的基因，发现了δ-6去饱和酶FADS2。FADS2 的缺失降低了体内的致瘤性和细胞增殖。在临床样本中，FADS2 在癌细胞中表达，而在基质细胞中不表达。抑制 FADS2 还能降低细胞的迁移和成球能力，增加细胞凋亡和铁凋亡标志物。脂质体检测显示，FADS2-敲除细胞中甘油三酯和胆固醇酯水平降低。FADS2敲除细胞的耗氧量比率也有所下降。这些数据表明，FADS2耗竭会导致脂质水平降低，从而减少能量的产生并减轻癌细胞的恶性程度。

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来源期刊

Cancer Science 医学-肿瘤学

自引率

3.50%

发文量

406

审稿时长

2 months

期刊介绍： Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports. Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.

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